The expression of SPINT2 gene is regulated by its methylation status, and the methylation status of SPINT2 is altered by HPV infection. The aberrant methylation status of SPINT2 gene may play an important role in the development of cervical cancer.

aberrant methylation of the SPINT2 gene is frequently observed in high-grade gliomas and might confer MET signaling in the glioma cells.

finding of only one heterozygous SPINT2 mutation in 19 patients with isolated CA/GA was not statistically significant

In this work, KLK14 binding to either hepatocyte growth factor activator inhibitor type-1 (HAI-1) or type-2 (HAI-2) was essayed using homology modeling, molecular dynamic simulations and free-energy calculations through MM/PBSA and MM/GBSA. KLK14 was successfully modeled.

limited role for HAI-2 in the inhibition of matriptase and prostasin is the result of its primarily intracellular localization in basal and spinous layer keratinocytes, which probably prevents the Kunitz inhibitor from interacting with active prostasin or matriptase

that the HAI-2 Kunitz domain 1 mutants influence the flux of matriptase to the plasma membrane by affecting the oligomerization, maturation and/or folding of matriptase

Our data indicate that hypoxic inhibition of JMJD3 activity reduces demethylation of H3K27me3, nucleosome removal, and hence induction of the STAT6 target gene CCL18, while induction of other STAT6-inducible genes such as SPINT2 remained unaffected by JMJD3.

Concomitant presence of TMPRSS13 with HAI-2 mediates phosphorylation of residues in the intracellular domain of the protease, and it coincides with efficient transport of the protease to the cell surface and its subsequent shedding.

This study presented a molecular characterization of congenital tufting enteropathy Italian patients, and identified one mutation in the SPINT2 gene

a missense mutation in the serine protease inhibitor SPINT2 may have a role in congenital sodium diarrhea

results suggest that the SPINT2 underexpression in the MSC from MDS patients is probably involved in the adhesion of progenitors to the bone marrow niche, through an increased HGF and SDF-1 signaling pathway.

Intestines of HAI-2 deficient mice showed altered expression of epithelial junctional proteins, including reduced levels of EpCAM, E-cadherin, occludin, claudin-1 and -7, as well as an increased level of claudin-4, indicating that the loss of HAI-2 compromises intestinal epithelial barrier function.

HAI-1 regulates the activity of activated matriptase, whereas HAI-2 has an essential role in regulating prostasin-dependent matriptase zymogen activation.

mutations in Prss8 restored placentation and normal development of HAI-1-deficient embryos and prevented early embryonic lethality, mid-gestation lethality due to placental labyrinth failure, and neural tube defects in HAI-2-deficient embryos.

HAI-1 and -2 are overexpressed in the liver in cholangiopathies with ductular reactions and are possibly involved in liver fibrosis and hepatic differentiation.

Unlike HAI-1 and matriptase, HAI-2 expression is detected in non-epithelial cells of brain and lymph nodes, suggesting that HAI-2 may also be involved in inhibition of serine proteases other than matriptase

Inhibition of the transmembrane serine protease matriptase (encoded by St14) is an essential function of HAI2 during tissue morphogenesis.

SPINT2 Protein Überblick

Protein Überblick

This gene encodes a transmembrane protein with two extracellular Kunitz domains that inhibits a variety of serine proteases. The protein inhibits HGF activator which prevents the formation of active hepatocyte growth factor. This gene is a putative tumor suppressor, and mutations in this gene result in congenital sodium diarrhea. Multiple transcript variants encoding different isoforms have been found for this gene.